Clinical Trial Dilemma: Save Lives Now — or Later?

An excellent front-page story by Amy Harmon in Sunday’s New York Times told a heart-rending tale of two cousins. Thomas McLaughlin, 24, was given a promising experimental drug to fight his life-threatening skin cancer in a clinical trial. He called it his “superpill” and his melanoma receded. But his cousin, Brandon Ryan, 22, had the bad luck of being assigned by computer lottery to the trial’s control group, receiving only standard chemotherapy. Even after the trial ended, Roche, the company that is developing the new drug, refused to offer legally permitted “compassionate access” to the drug to Ryan, apparently for fear of distorting the survival statistics needed to get rapid FDA approval. Ryan died in June, while McLaughlin is still taking the medication, known as PLX4032. (More on Time.com: Childhood Cancer Has Its Gold-Ribbon Day)

When told this way, the narrative seems straightforward: a story of evil drug companies and heartless federal bureaucrats, with each detail of the cousins’ lives an indictment of the callousness and inhumanity of science and the American health care system. But there’s another side to the dilemma, one that inevitably gets short shrift in the face of compelling cases like that of these cousins.

And that is, if you follow the debate over health care reform, you’ll see numerous questions about whether the FDA is approving drugs that don’t really work. Without well-designed randomized controlled trials, it’s impossible to truly know whether PLX4032 extends life or just shrinks tumors for a short period of time.

As the Times reported, it’s already known that the drug doesn’t keep tumors at bay indefinitely — sometimes, the respite it brings lasts only a few months. While that in itself could be a wonderful improvement in quality of life for someone who is dying, knowing whether or not a drug extends life is actually important.

Some researchers argue that new drugs like PLX4032 that shrink tumors with minimal side effects by targeting a specific gene are such an advance on grueling chemotherapy that randomized trials are simply cruel and unnecessary. The Times reports:

With chemotherapy, you’re subjecting patients to a toxic treatment, and the response rates are much lower, so it’s important to answer ‘Are you really helping the patient?'” said Dr. Charles L. Sawyers, chairman of human oncology at Sloan-Kettering. “But with these drugs that have minimal side effects and dramatic response rates, where we understand the biology, I wonder, why do we have to be so rigorous? This could be one of those defining cases that says, ‘Look, our system has to change.'”

Dr. Richard Pazdur, director of the cancer drug office at the Food and Drug Administration, said in a recent interview that the new wave of drugs in development — especially for intractable cancers like melanoma — might require individual evaluation. “This is an unprecedented situation that will, hopefully, be increasingly common, and it may require a regulatory flexibility and an open public discussion,” he said.

The moral dilemma faced by researchers and physicians who see cousins randomized to different fates is not simple — but it’s important to remember that without good data, there are many other lives at stake, too. The role of economic factors in creating such conflicts — in this case, Roche’s determination to get the drug approved for the largest group of patients ahead of competitors may have been part of the reason why Ryan was denied the drug — also needs to be considered. (More on Time.com:Can Eating Vegetables Prevent Lung Cancer?)

When AIDS first hit, activists stormed the FDA, pushing for “drugs into bodies” now and working tirelessly to change agency policy. The time it took for the FDA to approve drugs for life-threatening illnesses soon declined from 10 years to three years.

But as the activists became more educated about the science behind clinical trials — and as drugs with many difficult side effects and not too much evidence about their benefits were introduced — they became more cautious and concerned about data. Finding the balance between approving drugs fast enough to save lives immediately at risk — while studying them closely enough to avoid approving drugs that don’t work or even do harm — is extremely tricky.

And, because of the way we empathize and think about others, our minds much more easily focus on one or two people at risk now — rather than thousands later. Studies find that people are much more likely to give to charity if they are presented with the story of one sick child, rather than statistics about thousands who are ill.

Threading the needle between wrongly approving dangerous drugs in a rush to market and holding up lifesaving medications with deadly delays is far from easy — and our natural bias toward understanding and believing in anecdotes rather than data make it even harder. There are no easy answers.